Obesity, insulin resistance, atherosclerosis and hyperlipidemia are interrelated traits that have a significant impact upon morbidity and mortality. To better understand the relationship between these traits and the genes, which underlie them, we are developing a mouse model that utilizes the synteny between mouse chromosomes 2 to human chromosomes 20. Here three congenic mouse strains were created each of which contains 30 cM of DNA from chromosome 2 from the obesity resistant, insulin resistant CAST strain introgressed onto the background of an insulin resistant, obesity susceptible BL6 strain. Comparing the congenic mouse strains to the parental BL6 strain permits us to ask questions regarding the genes, which underlie the relevant traits. More importantly this comparison will allow us to investigate the interacting pathways involved. Specifically, this project aims to characterize the metabolic impact that each CAST locus has upon the BL6 background by identifying variations in body mass, fat distribution, bone density, insulin sensitivity and production, atherosclerosis and lipid profiles. Diets that enhance one or more of these traits will also be used to further assess the metabolic effect of each CAST locus. Concurrently global comparisons of gene expression using microarray analysis from adipose, muscle, pancreas and liver tissues will be performed to assess the contributions that specific genes within each congenic region make to the metabolic variations identified above. Relevant pathways will be identified utilizing the commercially available software (GeneSpring) designed to correlate gene expression profiles with pathways cited in the literature (KEGG).